We published the tumor modeling we did for dacomitinib in Clinical Pharmacology and Therapeutics: Pharmacometrics and Systems Pharmacology.

Link to Paper: doi:10.1002/psp4.12841

Fostvedt LK, Nickens DJ, Tan W, Parivar K. Tumor growth inhibition modeling to support the starting dose for dacomitinib. CPT Pharmacometrics Syst Pharmacol. 2022;11:1256-1267.

Abstract:

Dacomitinib is a second-generation, irreversible EGFR tyrosine kinase inhibitor for first-line treatment of patients with metastatic non-small cell lung cancer and EGFR-activating mutations. A high rate of dose reductions in the pivotal trial led to an observed inverse exposure-response (ER) relationship with the primary end points. Three ER models were developed to determine if the starting dose from the pivotal trial, 45 mg once daily (q.d.) dose, is appropriate: a longitudinal logistic regression model for adverse event-related dose changes, a Claret tumor growth inhibition (TGI) model, and a Cox model for progression-free survival (PFS) based on the TGI model predictions. This analysis included …

We published the Platelet modeling for abrocitinib, primarily work performed by Jessica Wojciechowski, in the British Journal of Clinical Pharmacology.

Link to Manuscript: https://doi.org/10.1111/bcp.15334

Citation: Wojciechowski J, Malhotra BK,Wang X, Fostvedt L, Valdez H, Nicholas T. Population pharmacokinetic-pharmacodynamic modelling of platelet time-courses following administration of abrocitinib. Br J ClinPharmacol. 2022;88(8):3856‐3871. doi:10.1111/bcp.15334WOJCIECHOWSKIET AL.3869

Abstract:
Aims
Abrocitinib is a selective Janus kinase 1 inhibitor for the treatment of moderate-to-severe atopic dermatitis. Herein we describe the time-course of drug-induced platelet reduction following abrocitinib administration, identify covariates affecting platelet counts, and determine the probability of patients experiencing thrombocytopaenia while receiving abrocitinib.

Methods
This analysis included data from two Phase 2 and three Phase 3 studies in psoriasis and atopic dermatitis patient populations administered abrocitinib 10–400 mg QD orally for up to 12 weeks, with platelet counts determined up to week 16. A semi-mechanistic model was developed to assess the impact of baseline platelet …

We published the population PK model, developed primarily by Jessica Wojciechowski, in Clinical Pharmacokinetics. I later expanded the model using Jess’s model as the foundation (unpublished).

Link to Article: https://doi.org/10.1007/s40262-021-01104-z

Citation: Wojciechowski, J., Malhotra, B.K., Wang, X. et al. Population Pharmacokinetics of Abrocitinib in Healthy Individuals and Patients with Psoriasis or Atopic Dermatitis. Clin Pharmacokinet 61, 709–723 (2022). https://doi.org/10.1007/s40262-021-01104-z

For my masters degree, I worked on a project evaluating random graphs and showed that an algorithm to count all the links in an erased configuration model scaled linearly depending on some conditions.

ITCS ’14: Proceedings of the 5th conference on Innovations in theoretical computer science. January 2014 Pages 225–234https://doi.org/10.1145/2554797.2554819

Citation (authorship is alphabetical): Berry JW, Fostvedt LK, Nordman DJ, Phillips CA, Seshadhri C, Wilson AG. Why do simple algorithms for triangle enumeration work in the real world?. InProceedings of the 5th conference on Innovations in theoretical computer science 2014 Jan 12 (pp. 225-234).

Abstract:

Triangle enumeration is a fundamental graph operation. Despite the lack of provably efficient (linear, or slightly super-linear) worst-case algorithms for this problem, practitioners run simple, efficient heuristics to find all triangles in graphs with millions of vertices. How are these heuristics exploiting the structure of these special graphs to provide major speedups in running …

I worked on the re-approval of Mylotarg supporting some of the modeling activities. We published this work in 2019 in Clinical Pharmacology and Therapeutics.

Link to Article: https://doi.org/10.1002/cpt.1500

Citation: Fostvedt LK, Hibma JE, Masters JC, Vandendries E, Ruiz‐Garcia A. Pharmacokinetic/pharmacodynamic modeling to support the re‐approval of gemtuzumab ozogamicin. Clinical Pharmacology & Therapeutics. 2019 Nov;106(5):1006-17.

Abstract

Gemtuzumab ozogamicin (Mylotarg; Pfizer, New York, NY) was the first antibody–drug conjugate to be approved for CD33-positive acute myeloid leukemia (AML). However, it was voluntarily withdrawn from the US market due to lack of clinical benefit in the confirmatory phase III trial. In 2012, several investigator cooperative studies using a different dosing regimen showed efficacy, but pharmacokinetic (PK) data were not collected in these trials. Through simulation of expected concentrations for new dosing regimens, PK/pharmacodynamic modeling was able to support the safety and efficacy of these regimens. Significant exposure–response relationships were found for the …